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The article discusses information on the snowboarding tour in Stockholm, Sweden. This travel report featuring the snowboarders entourage of Russell Dalby, Jeremy Cloutier, P-O Houde, Yale Cousino, and Will Demers, describes the weather conditions of Stockholm, and the revival of snowboarding interest through pro snowboarder Kareem El Rafie. The author also explains that the relaxed attitude that Swedes have regarding the use of public and private property is supported by law. He highlights the rail riding session in the district of Soderhallarna.

Cells from the mononuclear phagocyte system (MPS) act as systemic and local amplifiers that contribute to the progression of chronic inflammatory disorders. Transforming growth factor-β–activated kinase 1 (TAK1) is a pivotal upstream mitogen-activated protein kinase-kinase-kinase acting as a mediator of cytokine expression. It remains critical to determine in vivo the implication of TAK1 in controlling the innate immune system. Here, we describe a vehicle tailored to selectively deliver siRNAs into MPS cells after intravenous administration, and validate in vivo the potential of the RNAi-mediated TAK1 knock down for immunomodulation. In a mouse model of immune-mediated inflammatory disorder, we show that anti-TAK1 siRNA lipoplexes efficiently alleviate inflammation, severely impair the downstream c-Jun N-terminal kinase and nuclear factor-κB signaling pathways, and decrease the expression of proinflammatory mediators. Importantly, the systemic TAK1 gene silencing decreases the frequency of Th1 and Th17 cells, both mediating autoimmunity in experimental arthritis, demonstrating the immunomodulatory potential of TAK1. Finally, in vitro inhibition of TAK1 in myeloid cells decreases interferon-γ–producing T cells, suggesting that a delivery sys-tem able to target MPS cells and to silence TAK1 impacts on pathogenic T effector cells in autoimmunity.

The article discloses the role of endorphin in causing adrenaline rush to extreme sportsmen. An endorphin, known as endogenous morphine, improves the positive thinking caused by excitement felt by people while it eliminates pain in various parts of the brain and the spinal cord. A study in Bonn, Germany in 2008 revealed that exercise can generate endorphins into the brain.

Dopamine D2 receptor blockade has been an obligate mechanism of action present in all medications that effectively treat positive symptoms of schizophrenia (e.g., delusions and hallucinations) and have been approved by regulatory agencies since the 1950s. Blockade of 5-hydroxytrypatmine2Areceptors plays a contributory role in the actions of the second generation of antipsychotic drugs, the so-called atypical antipsychotics. Nevertheless, substantial unmet medical needs remain for the treatment of negative symptoms and cognitive dysfunction. Recognition that dissociative anesthetics block the N-methyl-d-aspartate (NMDA) receptor channel has inspired a search for glutamatergic therapeutic mechanisms because ketamine and phencyclidine are known to induce psychotic-like symptoms in healthy volunteers and exacerbate the symptoms of patients with schizophrenia. Current pathophysiological theories of schizophrenia emphasize that hypofunction of NMDA receptors at critical sites in local circuits modulate the function of a given brain region or control projections from one region to another (e.g., hippocampal-cortical or thalamocortical projections). The demonstration that a metabotropic glutamate 2/3 (mGlu2/3) receptor agonist prodrug decreased both positive and negative symptoms of schizophrenia raised hopes that glutamatergic mechanisms may provide therapeutic advantages. In addition to discussing the activation of mGlu2 receptors with mGlu2/3 receptor agonists or mGlu2 receptor positive allosteric modulators (PAMs), we discuss other methods that may potentially modulate circuits with hypofunctional NMDA receptors such as glycine transporter inhibitors and mGlu5 receptor PAMs. The hope is that by modulating glutamatergic neurotransmission, the dysfunctional circuitry of the schizophrenic brain (both local circuits and long-loop pathways) will be improved.

The article discusses that snowboarders should know what to expect and do after having an accident, and while waiting for the doctor's diagnosis to be given about the health condition. It states that in 2006, a study suggests that specifically designed audiotapes aid in the rehabilitation of patients. It also mentions that wanting to be healed immediately is not merely in the mind, physical work and exercise matter as well.

The article presents the construction of the lone corrugated culvert project ion Sproatt Mountain in British Columbia by the snowboarders Westbeach team. It mentions that the installation of the lone corrugated culvert took 10 hours plus nights of work for the team. Snowboarder Matt Belzille, one of the members of the team, claims that getting a good line for the culvert is difficult because it has a banked turn in the runway and the drop at the end was too high to a flat landing.

A personal narrative is presented which explores the author's travel experience along with the crew of Brothers Factory films from Calgary, Alberta to South Lake City, Utah.

A personal narrative is presented which explores the author's experience on snowboarding event Spain.

This article presents an interview with snowboarder Priscilla Levac. Levac discusses what its like to be filming for Standard in 2008. She discusses the challenges that she faced in doing the snowboarding film. When asked what she thinks about the expectations put on female professional snowboarders, Levac states the there should be high expectations on girls because girls can do some legit stuff.

The article profiles Etienne Gilbert, a snowboarder from St-Redempteur, Quebec. He joined the 418 crew for pipe sessions at Blackcomb Glacier in British Columbia. His laissez-faire outlook allowed him to enjoy life in the mountains and have fun while staying focused on progression. He won The Boardroom Slopestyle and Winter Love Big Air contests.

The author profiles snowboarder Matt Beardmore of Revelstoke, British Columbia. He describes Beardmore's personal background, the source of his snowboarding inspiration, and the motivation provided by his friend Keith Martin. The author also highlights Beardmore's work ethic, skills, riding style, key achievements, and his efforts to deal with an injury and extreme setbacks.

Cortical metabotropic glutamate receptors (mGluRs) seem to be involved in habituation of simple stimulus-bound behaviors (e.g., habituation to acoustic startle or odor-elicited orienting response). Habituation deficits may contribute to the cognitive symptoms of schizophrenia. In the present study, male NMRI mice were injected with mGluR2/3 antagonist 2S-2-amino-2-(1 S,2 S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY-341495) 30 min before being placed into novel arenas for automatic motor activity recording (2-h sessions). Administration of LY-341495 (1–10 mg/kg s.c.) dose-dependently prevented the habituation of the locomotor activity. Effects of LY-341495 (10 mg/kg) were fully and dose-dependently reversed by i.p. administration of haloperidol (0.03–0.3 mg/kg), clozapine (1–10 mg/kg), risperidone (0.01–0.1 mg/kg), olanzapine (0.3–3 mg/kg), aripiprazole (1–10 mg/kg), and sulpiride (3–30 mg/kg), each of which was given 15 min before the test. Effects of antipsychotic drugs were observed at the dose levels that did not affect spontaneous motor activity. LY-341495-induced delayed hyperactivity was also partially attenuated by lithium (50–200 mg/kg), amisulpride (1–10 mg/kg), and the selective dopamine D3 antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolin-ecarboxamide (SB-277011A; 3–30 mg/kg). Application of diazepam, imipramine, or several agonists and/or antagonists acting at various receptors that are thought to be relevant for antipsychotic treatment [e.g., 5-hydroxytryptamine (5-HT)2A, 5-HT3, and 5-HT6antagonists; 5-HT1Aagonist; D4 antagonist; CB1 antagonist; ampakines; and glycine transporter inhibitor) had no appreciable effects. Thus, behavioral deficits induced by mGluR2/3 blockade (such as delayed motor hyperactivity) are selectively reversed by clinically used antipsychotic drugs.

Tendons and ligaments are related connective tissues that join muscle to bone and bone to bone, respectively. Tendon and ligament injuries are widely distributed clinical problems in society and while healing of such disorders can occur, the original biological properties of the tissue do not return to normal. In this review, recent work on tendon and ligament development and the use of growth factors for successful cellular therapy of tendon and ligament disorders are discussed. In addition, anti-inflammatory concepts for the treatment of tendon and ligament injuries and recent developments in stem cell engineering for tendon and ligament tissues are examined. Lastly, gene transfer strategies for therapeutic applications to heal tendon and ligament disorders are reviewed.

Deferasirox (Exjade, ICL670) is an orally active iron chelator. Two molecules of deferasirox can form a complex with ferric iron (Fe-[ICL670]2) that can be excreted, reducing body iron overload. The blood binding parameters across species and the interaction with human serum albumin were analyzed for deferasirox and its iron complex. Both molecules were very highly bound to plasma proteins in all the tested species with unbound fractions in plasma in the range of 0.4 to 1.8% and 0.2 to 1.2% for deferasirox and Fe-[ICL670]2, respectively; binding of the iron complex was either similar or higher in all the species. The high plasma protein binding was in line with a distribution mainly into the plasma fraction of blood; the fraction in plasma was around 100% for Fe-[ICL670]2in all the species and 65 to 95% for deferasirox depending on the species. Investigations with isolated proteins pointed to serum albumin as the principal binding protein for deferasirox and its iron complex in human plasma. Competition binding experiments indicated that deferasirox at high concentrations displaced markers from the two main drug binding sites of human albumin, whereas Fe-[ICL670]2displaced only warfarin. In the context of the pharmacokinetic properties of deferasirox and Fe-[ICL670]2, the data indicate the importance of plasma protein binding for their disposition and support a comparison of the pharmacokinetics of deferasirox and its iron complex across species. The low likelihood of clinically relevant drug displacement by deferasirox in plasma is discussed.

In vitro studies: In CaCo‐2 cell monolayers the β‐nonapeptide H(β‐HAla‐β‐HLys‐β‐HPhe)3‐OH·4HCl (1), 14C‐labeled on both C atoms of the CH2–CO moiety of the central β‐HPhe residue, showed a low intrinsic permeability (<1%) and is subject to a prominent efflux system. The β‐peptide (1) binds to human and rat plasma protein in vitroindependent of the concentration of 1and of the species (30–36% bound fraction at 50, 500, and 5000 ng/ml), and has only low affinity for the corresponding blood cells (less than 5% of compound 1in blood cells).

The BMP2-dependent onset of osteo/chondrogenic differentiation in the acknowledged pluripotent murine mesenchymal stem cell line (C3H10T1/2) is accompanied by the immediate upregulation of Fibroblast Growth Factor Receptor 3 (FGFR3) and a delayed response by FGFR2. Forced expression of FGFR3 in C3H10T1/2 is sufficient for chondrogenic differentiation, indicating an important role for FGF-signaling during the manifestation of the chondrogenic lineage in this cell line. Screening for transcription factors exhibiting a chondrogenic capacity in C3H10T1/2 indentified that the T-box containing transcription factor Brachyury is upregulated by FGFR3-mediated signaling. Forced expression of Brachyury in C3H10T1/2 was sufficient for differentiation into the chondrogenic lineage in vitro and in vivo after transplantation into muscle. A dominant-negative variant of Brachyury, consisting of its DNA-binding domain (T-box), interferes with BMP2-mediated cartilage formation. These studies indicate that BMP-initiated FGF-signaling induces a novel type of transcription factor for the onset of chondrogenesis in a mesenchymal stem cell line. A potential role for this T-box factor in skeletogenesis is further delineated from its expression profile in various skeletal elements such as intervertebral disks and the limb bud at late stages (18.5 d.p.c.) of murine embryonic development.

The anticonvulsant activity of inhibitors of monoamine oxidase (MAO) was reported early after the development of irreversible MAO inhibitors such as tranylcypromine, but was never clinically used because of the adverse effects of these compounds. The more recently developed reversible MAO inhibitors with selectivity for either the MAO-A or MAO-B isoenzyme forms have not been studied extensively in animal models of epilepsy, so it is not known which type of MAO inhibitor is particularly effective in this respect. We compared the following drugs in the kindling model of epilepsy: 1) l-deprenyl (selegiline), i.e., an irreversible inhibitor of MAO-B, which, however, also inhibits MAO-A at higher doses, 2) the novel reversible MAO-B inhibitor LU 53439 (3,4-dimethyl-7-(2-isopropyl-1,3,4-thiadiazol-5-yl)-methoxy-coumarin), which is much more selective for MAO-B than l-deprenyl, 3) the novel reversible and highly selective MAO-A inhibitor LU 43839 (esuprone; 7-hydroxy-3,4-dimethylcoumarin ethanesulfonate), and 4) the irreversible nonselective MAO inhibitor tranylcypromine. Esuprone proved to be an effective anticonvulsant in the kindling model with a similar potency as l-deprenyl. In contrast to esuprone and l-deprenyl, the selective MAO-B inhibitor LU 53439 was not effective in the kindling model; this substantiates the previous notion that the anticonvulsant activity ofl-deprenyl is not related to MAO-B inhibition, but to other effects of this drug, such as inhibition of MAO-A. Drugs inhibiting both MAO-A and MAO-B to a similar extent (tranylcypromine) or combinations of selective MAO-A and MAO-B inhibitors (esuprone plus LU 53439) had no advantage over MAO-A inhibition alone, but were less well tolerated. The data thus suggest that selective MAO-A inhibitors such as esuprone may be an interesting new approach for the treatment of epilepsy.

Transfer of a 36-kilobase piece of human DNA containing the β-interferon (IFN-β) gene into mouse Ltk−cells leads to transient expression of human interferon even without an exogenous inducer. A low level of human interferon expression is also found in most stable clones containing the transferred DNA. With double-stranded RNA or Newcastle disease virus (NDV) as inducer, human interferon expression is greatly increased. The induced transcript is identical to normal human IFN-β mRNA. Neighbouring genes contained on the transferred DNA are co-induced but are not essential for the production of human interferon in mouse L cells.

The mechanism responsible for the antihypertensive effect of urapidil is not yet completely understood. Its vasodilator action has been attributed to an antagonism at vascular a1-adrenoceptors. However, it has been suggested that a central action contributes to the hypotensive effect. Recently, three potent analogues of urapidil have been described which also lower blood pressure by a central mechanism. 5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype have been implicated with the central control of cardiovascular function. In the present study, the affinities of these urapidil derivatives (5-acetyl, 5-formyl- and 5-methylurapidil) for 5-HT receptors were investigated using 3H-8-hydroxy-2-(di-n-propylamino)tetralin (3H-8-OH-DPAT), 125I-iodocyanopindolol (125I-ICYP) and 3H-ketanserin for labelling 5-HT1A, 5-HT1B and 5-HT2 binding sites, respectively. 3H-Prazosin and 3H-clonidine were used as selective a1- and a2-adrenoceptor radioligands, respectively. Urapidil and its analogues produced half-maximum inhibition of 3H-8-OH-DPAT binding at concentrations of 4 × 10-9 mol/l to 4 × 10-7 mol/l with the following order of potency: urapidil < 5-acetyl- < 5-formyl- < 5-methyl-urapidil. Thus, 5-methyl-urapidil is one of the most potent ligands at 5-HT1A recognition sites known to date. The IC50 values of urapidil and its derivatives for 3H-prazosin binding were in the range of 5 × 10-8 mol/l to 8 × 10-7 mol/l (order of potency: urapidil < 5-formyl- < 5-acetyl- = 5-methyl-urapidil). The affinity of these analogues for 5-HT1B, 5-HT2 and a2-adrenergic recognition sites was distinctly lower. Urapidil and its congeners clearly discriminate between 5-HT- and between a-receptor subtypes. It is postulated that the high affinity for 5-HT1A receptors as well as for a1-adrenoceptors is relevant to the hypotensive properties of these compounds.

The influence of thyroid hormones on the concentration and properties of a1-adrenoceptors in a crude membrane fraction obtained from the rat cerebral cortex was investigated using the [3H]-WB 4101 binding assay. Animals were made hypothyroid by feeding 6-propyl-2-thiouracil for 8 weeks. Hyperthyroidism was induced by triiodothyronine injections (50 µg/100 g body weight) for 9 days.1.The binding of [3H]-WB 4101 was saturable and of high affinity in controls as well as in hyper- and hypothyroid animals. The maximal number of binding sites (Bmax), which amounted to 95 fmol/mg protein in control animals, was increased by 27% in cortical membranes from hyperthyroid rats and reduced by 23% in the hypothyroid group.2.The reduction in [3H]-WB 4101 binding due to 6-propyl-2-thiouracil feeding was reversible by triiodothyronine treatment.3.Dissociation constants (KD) calculated from saturation experiments (0.25 nM) or kinetic data (0.21 nM) remained unchanged in altered thyroid states.4.Inhibition of [3H]-WB 4101 binding by adrenergic agonists and antagonists revealed no differences between euthyroid and hypothyroid animals. The higher affinity of prazosin to the binding sites compared with yohimbine indicated that [3H]-WB 4101 predominantly labeled a1-adrenoceptors.

Literaturhinweise und eigene Beobachtungen führen zu der Annahme, daß ein pathogenetischer Zusammenhang zwischen Ostitis deformans Paget, Pseudoxanthoma elasticum (Darier) und Angioid streaks (Knapp) besteht. Auf Grund widersprechender Untersuchungsergebnisse wird eine Überprüfung der Zusammenhangsfrage empfohlen.